Development of Plowast-monodentate diamidophosphites with a C1-symmetric 1,2-diamine backbone: The effects of substituents in the 1,3,2-diazaphospholidine cycle on Pd-catalyzed asymmetric allylations

Article abstract of DOI:10.1016/j.tetasy.2013.02.010

We have designed and synthesized a small library of modular monodentate diamidophosphite ligands with stereogenic phosphorus atoms. The library was prepared efficiently from the commercially available and inexpensive (S)-N-Boc-amino acids. These novel ligands were screened in the Pd-catalyzed asymmetric allylations of (E)-1,3-diphenylallyl acetate with dimethyl malonate as the C-nucleophile with up to 93% ee being obtained. The results showed that the different substituents in the 1,3,2-diazaphospholidine cycle had remarkable effects on the enantioselectivity.

Full text of DOI:10.1016/j.tetasy.2013.02.010

Tetrahedron: Asymmetry xxx (2013) xxx–xxx
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Tetrahedron: Asymmetry
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Development of P⁄-monodentate diamidophosphites with a C1-symmetric
1,2-diamine backbone: the effects of substituents in the
1,3,2-diazaphospholidine cycle on Pd-catalyzed asymmetric allylations
Konstantin N. Gavrilov a, , Alexei A. Shiryaev a, Sergey V. Zheglov a, Oksana V. Potapova a,
⇑
Ilya V. Chuchelkin a, Ivan M. Novikov a, Eugenie A. Rastorguev b, Vadim A. Davankov b
a Department of Chemistry, Ryazan State University, 46 Svoboda Street, 390000 Ryazan, Russian Federation
b Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Street, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
We have designed and synthesized a small library of modular monodentate diamidophosphite ligands
with stereogenic phosphorus atoms. The library was prepared efficiently from the commercially available
and inexpensive (S)-N-Boc-amino acids. These novel ligands were screened in the Pd-catalyzed asymmet-
ric allylations of (E)-1,3-diphenylallyl acetate with dimethyl malonate as the C-nucleophile with up to
93% ee being obtained. The results showed that the different substituents in the 1,3,2-diazaphospholidine
cycle had remarkable effects on the enantioselectivity.
Received 28 January 2013
Accepted 15 February 2013
Available online xxxx
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
In recent years, phosphite-type chiral compounds have
emerged as extremely attractive ligands for many metal-catalyzed
The successful development of transition metal catalyzed asym-
metric processes over the last few decades has been largely steered
by the introduction of new chiral ligands. A chiral ligand is used to
both influence the reactivity of the metal and to direct the stereo-
chemical course of the catalyzed reaction. Due to the special metal
ligation properties of phosphorus derivatives, phosphorus-contain-
ing ligands play a major role as metal binders in asymmetric orga-
nometallic catalysis.1,2 Since the early 1970s, a large number of
such stereoselectors have been applied in many asymmetric cata-
lytic transformations. Virtually all available natural compounds, as
well as binaphthyl, biphenyl, and ferrocene derivatives, have been
used in the preparation of large libraries of different phosphorus-
based chiral ligands.3–16 The overwhelming majority of such
ligands in the composition of the corresponding metal complexes
is able to catalyze with different enantioselectivities either a cer-
tain type of chemical transformation, or one certain reaction. Only
so-called privileged ligands, rooted in a few core structures, can be
regarded as being truly successful in demonstrating proficiency in
various mechanistically unrelated reactions. These ligands are very
rare, and their cost significantly restrains their wide practical
use.16,17 As a result, the development of simple and efficient meth-
ods for the preparation of inexpensive ligands based on available
enantiopure synthons is still a relevant subject.16,18,19
asymmetric processes. First, they are easy to prepare from inex-
pensive feedstocks in large quantities through the use of relatively
simple condensation processes. Second, phosphite-type ligands are
less sensitive to air and other oxidizing agents than typical phos-
phanes. Hence, this makes it possible to develop protocols for the
whole process, including ligand synthesis, that do not necessitate
the use of a glove box. Furthermore, they are amenable to parallel
synthesis, even in solid phase synthesis. Such key advantages allow
the synthesis and screening of extensive libraries of structurally
diverse chiral ligands with the aim of obtaining high activities
and selectivities for each particular reaction. In addition, phos-
phite-type ligands are characterized by a highly modular structure
and pronounced p
-acceptor capacity.8,12,19–33
It should be noted that among the phosphite-type chiral
ligands, much attention has been focused on phosphites (three
P–O bonds) and phosphoramidites (two P–O bonds and one P–N
bond).8,12,17,19,20,24–26,34–36 Less research has been reported on the
synthesis and catalytic application of chiral diamidophosphite
ligands (one P–O bond and two P–N bonds).1,37–43 It is rather
important that these compounds have different properties from
phosphites or phosphoramidites. For example, nitrogen substitu-
ents create more steric bulk around the phosphorus than oxygen,
since nitrogen substitution may be greater. Furthermore, the
replacement of the oxygen atom in the first coordination sphere
of the phosphorus by a nitrogen atom increases the electron den-
sity on the phosphorus center.1,43
⇑
Corresponding author. Tel.: +7 4912 280580; fax: +7 4912 281435.
E-mail addresses: k.gavrilov@rsu.edu.ru (K.N. Gavrilov), hagehoge@mail.ru
Diamidophosphites with phospholidine rings and asymmetric
phosphorus atoms can be considered as very promising
(E.A. Rastorguev).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.02.010
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2
K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
stereoinducers. In particular, these compounds display balanced
be noted that these synthons are highly versatile and inexpensive
enantiopure raw materials. In the design of novel diamidophosph-
ites, we pursued ligand structures that contained a Ph-substituent
at one of the nitrogen atoms. It is known that the proximity of the
aryl group to the phosphorus atom is important in enhancing the
chiral space around the metal center.43 Treatment of 1a–e with
aniline in the presence of DCC (1,3-dicyclohexylcarbodiimide) as
electronic characteristics since they are both good
p-acceptors
ast
(due to the accessibility of low-lying
p
orbitals) as well as good
PN
r
-donors. The inclusion of the phosphorus atom in the five-mem-
bered ring enhances the resistance of the ligands to oxidation and
hydrolysis, while the possibility of varying the nature of the sub-
stituents on the nitrogen and phosphorus atoms allows control
over the steric and electronic parameters. Moreover, their modular
nature allows a facile systematic variation of the configuration of
the P⁄- and C⁄-stereocenters in the phospholidine rings.1,39,44,45 If
in this case the donor phosphorus atom is asymmetric, this signif-
icantly assists in the transfer of chirality in the key step of the
catalytic cycle. In the appropriate complexes, the asymmetric
phosphorus atom binds directly to the metal atom. This factor
provides a more efficient chiral environment at the site where
the enantioselection originates.4,17,46,47 The efficiency of these
ligands strongly depends on their framework. Thus, P⁄-mono and
P⁄,N-bidentate diamidophosphites with a phosphabicyclic skeleton
LA–D (Fig. 1)
were used successfully in Pd- and Ir-catalyzed asymmetric allyla-
tions, Rh-catalyzed asymmetric additions, and hydrogena-
tions.33,38,44,45,47–53 At the same time, monocyclic ligands LE and
LF appeared to be ineffective stereoselectors. Thus, practically race-
mic products were obtained with their use in Pd- and Ir-catalyzed
allylic alkylations with the participation of dimethyl malonate.54,55
Herein, we report the synthesis of a small series of P⁄-monoden-
tate diamidophosphites containing 1,3,2-diazaphospholidine rings
and based on C1-symmetric 1,2-diamines as advantageous precur-
sors. We also report the results of a direct comparison of these
stereoselectors in Pd-catalyzed asymmetric allylations of (E)-1,3-
diphenylallyl acetate. On the one hand, the enantioselective Pd-
catalyzed allylic substitution has emerged as a powerful synthetic
tool, which is tolerant of various functional groups in the substrate
and which operates with a wide range of nucleophiles. As a result,
the Pd-catalyzed allylic substitution is a versatile process that is
widely used in the total synthesis of enantiopure natural and
unnatural products.2,5,46,56–62 On the other hand, this is a common
benchmark test for initial ligand screening. From a functional point
of view, the enantiomeric excesses obtained are the simplest in-
dexes for evaluating new chiral ligands.2,61,63
a
coupling agent allowed isolation of the corresponding
carbamates 2a–e.64 Next, LiAlH4 reduction of 2a–e leads to (S)-
N2-methyl-N1-phenyl-1,2-diamines 3a–e with C1 symmetry. In
turn, 3a–e were used as simple and convenient starting materials
for the substituted 2-chloro-3-methyl-1-phenyl-1,3,2-diazaphosp-
holidines 4a–e as phosphorylating reagents (Scheme 1). Com-
pounds 4a–e containing the stereogenic phosphorus atoms were
obtained by reaction of the corresponding 1,2-diamine 3a–e and
PCl3 in benzene in the presence of Et3N as a base because of the
concomitant formation of HCl. Reagents 4a–e are stable on storage
under a dry atmosphere, can be easily purified by vacuum distilla-
tion, and can be prepared on a gram scale. Compounds 4a–e are
stereoindividual, since the 31P NMR spectra of their solutions in
CDCl3 exhibited narrow singlets at dP between 154.8 and 161.9.
The 1H and 13C NMR spectra were in agreement with those ex-
pected for these C1 compounds (see Section 4).
Reagents 4a–e readily and efficiently perform the phosphoryla-
tion. Compounds 4a–e reacted smoothly in toluene in the presence
of Et3N as a HCl scavenger with adamantan-1-ol or methanol
(Scheme 2). Diamidophosphites 5a–e and 6a,b were obtained in
rather good yields (77–90%), reflecting their stability during the
work-up and purification by distillation under vacuum or by flash
chromatography. Compounds 5a–e and 6a,b are either oils, waxy
solids, or liquids, which are readily soluble in common organic sol-
vents. They can also be stored under dry conditions at room tem-
perature over several months without any degradation. The
diamidophosphites 5a–e and 6a,b possess a 1,3,2-diazaphospholi-
dine ring, P⁄- and C⁄-stereocenters, and various substituents on
these chirogenic atoms. They were fully characterized by 1H, 13C,
and 31P NMR spectroscopy, MALDI TOF/TOF or EI mass spectrome-
try as well as by elemental analysis. The 31P NMR spectroscopic
data for 5a–e and 6a,b are summarized in Table 1. These diam-
idophosphites are mixtures of epimers with respect to the phos-
phorus stereocenter and contain 52–77% of the major epimers.
Ligands 5a–e with a bulky adamantyloxy exocyclic substituent at
the phosphorus atom contain smaller amounts of the minor
epimers. We did not establish the absolute configuration of the
P⁄-stereocenters in the structure of ligands 5a–e and 6a,b. Never-
theless, considering the data presented in the literature on the
related compounds LA (Fig. 1).33,45,48 it can be assumed that the
2. Results and discussion
The P⁄-chiral diamidophosphite ligands 5a–e and 6a,b were
prepared in two steps, starting from the corresponding 1,2-dia-
mines 3a–e, which are easily prepared from the commercially
available (S)-N-Boc-amino acids 1a–e (Schemes 1 and 2). It should
Ph
O
N
O
P
NR2
P
OAr
N
N
Ph
Ph
O
Ph
O
N
LC
LB
N
P
NR2
P
OR
N
O
N
8
Ph
LD
O
N
N
P
LA
N
P
Ts
LF
LE
Figure 1. P⁄-Chiral 1,3,2-diazaphospholidine and 1,3,2-oxazaphospholidine ligands.
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K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
3
+ C6H5NH2
O
O
H
N
+ LiAlH4
THF
+ PCl3
2.2 Et3N,C6H6
H
N
H
N
DCC, CH2Cl2
Ph
Ph
N
N
Boc
OH
Boc
N
H
N
H
P
Cl
R
R
- 2 Et3N . HCl
R
R
1a-e
2a-e
3a-e
4a-e
R = Bn a, sec-Bu b, tert-Bu c, i-Pr d, Ph e
Scheme 1. Synthesis of 1,2-diamines 3a–e and phosphorylating reagents 4a–e.
Ph
N
O
N
P
Ph
N
O
N
P
Ph
N
O
5e
N
P
5d
6a
Ph
N
HO
+
N
HO
P
+
N
N
O
Cl
P
1.1 Et3N, C6H5CH3
- Et3N . HCl
1.1 Et3N, C6H5CH3
- Et3N . HCl
R
5c
4a-e
Ph
N
Ph
N
N
P
N
P
O
Ph
8'
7'
N
O
6'
5'
N
P
5b
1'
6b
10'
9'
O
2'
4'
5a
3'
Scheme 2. Synthesis of P⁄-monodentate diamidophosphites 5a–e and 6a,b.
Table 1
major epimers of 5a,b,d,e and 6a,b have asymmetric phosphorus
atoms with an (S)-configuration. The 13C NMR spectra of (2S,5S)-
epimers of diamidophosphites LA are characterized by essentially
31P NMR chemical shifts (CDCl3) and cone angles
h
(deg.) of
ligands 5a–e and 6a,b
2
lower spin–spin coupling constants JC(8),P than the 13C NMR spec-
Ligand
dP
h
5a (38%)a
(62%)
5b (32%)
(68%)
5c (59%)
(41%)
5d (23%)
(77%)
5e (25%)
(75%)
6a (43%)
(57%)
6b (48%)
(52%)
117.5
116.2
120.3
115.1
130.2
115.6
121.0
115.6
117.1
115.1
126.1
117.6
127.8
116.0
185
2
tra of (2R,5S)-epimers. Analogously, the JN-CH3 values (13.6–
20.4 Hz) in the 13C NMR spectra of major epimers of 5a,b,d,e and
6a,b are considerably smaller than in the case of minor epimers
(29.5–41.0 Hz) (see Section 4). In the 31P NMR spectra of 5a,b,d,e
and 6a,b, their major epimers have the up-field resonances dP
115.1–117.6 (Table 1). On the contrary, the major epimer (59%)
of ligand 5c has a low-field signal dP 130.2, high coupling constant
2JN-CH3 = 45.3 Hz and, as a result, presumably an (R)-configuration
for the P⁄-stereocenter. In order to estimate the steric demands
of ligands 5a–e and 6a,b, we calculated their Tolman’s angles65
by the reported method, by using semi-empirical quantum-
mechanical AM1 techniques with full optimization of the geomet-
rical parameters.66 The results obtained (Table 1) show that the
steric demands (h) of 5a–e and 6a,b vary over a wide range be-
tween 134° and 193°, peaking at diamidophosphites 5a and 5e.
Phosphacyclanes 6a and 6b with P-OMe fragments are character-
ized by moderate steric demands (h = 140° and 134°, respectively),
151
174
166
193
140
134
a
Percentage of P⁄-epimers.
while 5b (h = 151°) and especially 5a and 5c–e (h = 166°–193°),
bearing adamantyl groups, appear to be substantially more bulky
ligands.65,67
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4
K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
With these ligands with pronounced structural diversity in
stereoselectors: enantioselectivities of up to 40% and 69% ee were
observed for these ligands. The best asymmetric induction was
achieved with L/Pd = 2. The reaction in THF was more enantioselec-
tive, while a higher conversion was achieved in CH2Cl2 (Table 3,
entries 5–8 and 13–16). The effect of the substituent at the
C⁄-stereocenter was also studied with a pair of less bulky diam-
idophosphite ligands 6a and 6b. The best activities and enantiose-
lectivities were obtained using phosphacyclane 6b, which contains
a sec-Bu-substituent (Table 3, 21–24 and 25–28). This behavior is
in contrast with the substituent effect observed for the related pair
of 5a and 5b, for which the enantioselectivity was higher when a
Bn-substituent was present. Remarkably, all ligands 5a–e and
6a,b promoted formation of the (R)-enantiomer of malonate 8b.
The novel diamidophosphites were next evaluated in the Pd-
catalyzed allylic amination of 7 with pyrrolidine as the N-nucleo-
phile. In most experiments, 5a–e and 6a,b demonstrated excellent
conversion, but mediocre levels of asymmetric induction (up to
50% ee, Table 4). With regards to the enantioselectivity, the influ-
ence of the nature of the substituent at the C⁄-stereocenter follows
the following trend: tert-Bu 5c (up to 50% ee, entry 10) > i-Pr 5d
(up to 47% ee, entry 16) > Bn 5a (up to 40% ee, entry 4) > Ph 5e
(up to 37% ee, entry 20) > sec-Bu 5b (up to 31% ee, entry 8) and
sec-Bu 6b (up to 39% ee, entry 28) > Bn 6a (up to 19% ee, entry
23). In most cases THF as the reaction medium and a molar ratio
L/Pd = 2 are undoubtedly preferable, but the catalytic process with
hand, we studied their reactivities and enantioselectivities in the
Pd-catalyzed asymmetric allylations of (E)-1,3-diphenylallyl ace-
tate 7. As stated above, the latter was chosen as a substrate because
this model process is very convenient for the direct comparison of
the efficiency of the different stereoselectors. The catalysts were
generated in situ from [Pd(allyl)Cl]2 and the ligands at 1:1 and
2:1 L/Pd molar ratios. In a first set of experiments, we tested the
new diamidophosphites in the allylic sulfonylation of 7 with so-
dium para-toluene sulfinate as an S-nucleophile, under standard
conditions and in THF as the solvent (Table 2). The results obtained
showed that the efficiency of these ligands differs dramatically. In
particular, sulfone (R)-8a was obtained in 98% yield and 75% ee
when diamidophosphite 5e with a Ph-substituent at the C⁄-stereo-
center was employed as the chiral auxiliary (Table 2, entry 9). For
5e, the L/Pd molar ratio had no effect on the reactivity or enanti-
oselectivity (see Table 2, entries 9 and 10). Compounds 5b, 5d,
6a, and 6b displayed moderate asymmetric induction (up to 48%,
59%, 42%, and 55% ee, respectively). The palladium catalysts de-
rived from ligands 5a and 5c showed excellent activity, but poor
enantioselectivity (no more than 19% ee, Table 2, entries 1, 2, 5,
and 6). It should be noted that in all cases, the catalytic systems
based on novel diamidophosphites led to product 8a with an (R)-
configuration.
On the contrary, in the Pd-catalyzed allylic alkylation of 7 with
dimethyl malonate as the C-nucleophile, diamidophosphites 5a
and 5c were found to be the most efficient stereoinducers, provid-
ing up to 93% and 70% ee, respectively. The enantiomeric excess
does not depend on the molar ratio of L/Pd. It is clear that CH2Cl2
is the solvent of choice in both cases (Table 3, entries 1–4 and
9–12). At the same time, ligand 5e afforded product (R)-8b with
low enantiomeric purity (up to 27% ee, Table 3, entries 17–20).
As in the case of the allylic sulfonylation, 5b and 5d are moderate
Table 3
Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate
7
with dimethyl
malonatea
MeO2C
CO2Me
Ph
OAc
Ph
CH2(CO2Me)2, cat
Ph
Ph
*
solvents
7
8b
Table 2
Pd-catalyzed allylic sulfonylation of (E)-1,3-diphenylallyl acetate 7 with sodium para-
toluene sulfinatea
Entry
Ligand
L/Pd
Solvent
Conversion (%)
eeb (%)
1
2
3
4
5
6
7
8
5a
5a
5a
5a
5b
5b
5b
5b
5c
5c
5c
5c
5d
5d
5d
5d
5e
5e
5e
5e
6a
6a
6a
6a
6b
6b
6b
6b
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
CH2Cl2
CH2Cl2
THF
100
99
34
100
52
100
20
47
35
86
0
90 (R)
93 (R)
7 (R)
46 (R)
9 (R)
30 (R)
11 (R)
40 (R)
65 (R)
70 (R)
—
THF
CH2Cl2
CH2Cl2
THF
OAc
Ph
THF
O
S
*
O
9
CH2Cl2
CH2Cl2
THF
NaSO2pTol, cat
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Ph
Ph
Ph
THF
THF
0
—
8a
7
CH2Cl2
CH2Cl2
THF
100
100
0
50
78
91
34
33
29 (R)
63 (R)
—
Entry
Ligand
L/Pd
Yield (%)
eeb (%)
THF
69 (R)
20 (R)
27 (R)
20 (R)
25 (R)
11 (R)
26 (R)
0
2 (R)
54 (R)
47 (R)
6 (R)
50 (R)
1
2
3
4
5
6
7
8
5a
5a
5b
5b
5c
5c
5d
5d
5e
5e
6a
6a
6b
6b
1
2
1
2
1
2
1
2
1
2
1
2
1
2
98
97
25
40
94
95
70
98
98
95
53
90
98
82
9 (R)
19 (R)
14 (R)
48 (R)
2 (R)
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
CH2Cl2
THF
100
100
25
3 (R)
55 (R)
59 (R)
75 (R)
74 (R)
42 (R)
7 (R)
THF
60
9
CH2Cl2
CH2Cl2
THF
100
100
100
100
10
11
12
13
14
THF
55 (R)
15 (R)
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room tempera-
a
ture for 48 h (BSA, KOAc).
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 in THF at room
b
The conversion of substrate 7 and enantiomeric excess of 8b were determined
by HPLC (Daicel Chiralcel OD-H, C6H14/i-PrOH = 99/1, 0.3 mL/min, 254 nm,
t(R) = 28.0 min, t(S) = 29.3 min).
temperature for 48 h.
b
Enantiomeric excess of 8a was determined by HPLC (Daicel Chiralcel OD-H,
C6H14/i-PrOH = 4/1, 0.5 mL/min, 254 nm, t(R) = 16.3 min, t(S) = 18.5 min).
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K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
5
Table 4
depends strongly on the nature of the nucleophile; (iv) as a whole,
the most sterically demanding phosphacyclanes 5e, 5a, and 5c
(h = 193°, 185° and 174°), bearing the adamantyl group, are the
best stereoselectors in the Pd-catalyzed allylic sulfonylations, alky-
lations, and aminations, respectively. The enantioselectivity ob-
tained with the less bulky diamidophosphites 6a and 6b was
poor or mediocre. Nevertheless, in some cases these ligands were
more efficient than the related compounds 5a and 5b. It is clear
that the asymmetric induction is powerfully affected by the sub-
stituents at the C⁄- and P⁄-stereocenters, the steric properties of
the ligands, and the nature of the nucleophile.
Pd-catalyzed allylic amination of (E)-1,3-diphenylallyl acetate 7 with pyrrolidinea
OAc
Ph
N
*
HN(CH2)4, cat
solvents
Ph
Ph
Ph
7
8c
Entry
Ligand
L/Pd
Solvent
Conversion (%)
eeb (%)
In general, P⁄-chiral monocyclic diamidophosphites with a
1,3,2-diazaphospholidine ring are very attractive for further
research due to their easy accessibility, stability, facile modular
construction, and because they are inexpensive. The availability
of many C1-symmetric 1,2-diamines makes ligand-tuning possible,
which allows the synthesis of many series of diamidophosphite
ligands that can be screened in transition metal catalyzed
asymmetric reactions for high activity and enantioselectivity. As
a result, such investigations are currently in progress in our
laboratories.
1
2
3
4
5
6
7
8
5a
5a
5a
5a
5b
5b
5b
5b
5c
5c
5c
5c
5d
5d
5d
5d
5e
5e
5e
5e
6a
6a
6a
6a
6b
6b
6b
6b
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
CH2Cl2
CH2Cl2
THF
100
100
100
100
100
100
32
61
83
100
82
61
100
100
100
100
100
100
77
100
100
100
50
100
100
100
100
100
2 (S)
4 (S)
20 (S)
40 (S)
2 (R)
THF
CH2Cl2
CH2Cl2
THF
3 (R)
13 (R)
31 (R)
40 (S)
50 (S)
17 (S)
49 (S)
0
THF
9
CH2Cl2
CH2Cl2
THF
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
THF
CH2Cl2
CH2Cl2
THF
2 (S)
4. Experimental
4.1. General
33 (S)
47 (S)
35 (R)
25 (R)
29 (S)
37 (S)
5 (R)
THF
CH2Cl2
CH2Cl2
THF
The 31P, 13C, and 1H NMR spectra were recorded with a Bruker
AMX 400 instrument (162.0 MHz for 31P, 100.6 MHz for 13C, and
400.13 MHz for 1H). The complete assignment of all the resonances
in 13C NMR spectra was achieved by the use of DEPT techniques.
Chemical shifts (ppm) were given relative to Me4Si (1H and 13C)
and 85% H3PO4 (31P NMR). Data are represented as follows: chem-
ical shift, multiplicity (br = broad, s = singlet, d = doublet, t = triplet,
m = multiplet), coupling constants in Hertz (Hz) integration. Mass
spectra were recorded with a Varian MAT 311 spectrometer (EI)
and a Bruker Daltonics Ultraflex spectrometer (MALDI TOF/TOF).
HPLC analyses were performed on Agilent 1100 and Stayer instru-
ments using ChiralcelÒ columns. Optical rotations were measured
on a Perkin–Elmer 341 polarimeter. Elemental analyses were per-
formed at the Laboratory of Microanalysis (Institute of Organoele-
ment Compounds, Moscow).
THF
CH2Cl2
CH2Cl2
THF
6 (R)
19 (R)
11 (R)
19 (S)
33 (S)
19 (S)
39 (S)
THF
CH2Cl2
CH2Cl2
THF
THF
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room tempera-
ture for 48 h.
b
The conversion of substrate 7 and enantiomeric excess of 8c were determined
by HPLC (Daicel Chiralcel OD-H, C6H14/i-PrOH/HN(Et)2 = 200/1/0.1, 0.9 mL/min,
254 nm, t(R) = 5.0 min, t(S) = 6.1 min).
All manipulations were carried out under a dry argon atmo-
sphere in flame-dried glassware and in freshly dried and distilled
solvents. For example, benzene, toluene, and tetrahydrofuran were
freshly distilled from sodium benzophenone ketyl before use;
dichloromethane was distilled from NaH. Triethylamine and pyr-
rolidine were distilled over KOH and then over a small amount of
LiAlH4 before use. Thin-layer chromatography was performed on
E. Merck pre-coated silica gel 60 F254 and Macherey-Nagel Alu-
gram Alox N/UV254 plates. Column chromatography was per-
formed using silica gel MN Kieselgel 60 (230–400 mesh) and
MN-Aluminum oxide, basic, Brockmann Activity 1. Carbamates
2a–e were synthesized using a modified literature procedure.64
All spectroscopic data for compounds 2a, 2d, 3d, and 3e were in
good agreement with the literature.64,69,70 Phosphorylating re-
agents 4a–e and ligands 5a–e, 6a,b were prepared analogously to
known procedures.45,49,71 [Pd(allyl)Cl]2 and starting substrate 7
were obtained as published.72 Pd-catalyzed allylic substitution:
sulfonylation of substrate 7 with sodium para-toluene sulfinate,
alkylation with dimethyl malonate, and amination with pyrroli-
dine were performed according to the appropriate procedures.49,73
(S)-N-Boc-amino acids 1a–e, DCC (1,3-dicyclohexylcarbodiimide),
aniline, adamantan-1-ol, dimethyl malonate, BSA (N,O-bis(trimeth-
ylsilyl) acetamide), and sodium para-toluene sulfinate were pur-
chased from Aldrich and Acros Organics and used without
further purification.
participation of 5c resulted in higher conversion and enantioselec-
tivity in CH2Cl2. In the allylic amination of substrate 7, not only dif-
ferent stereoinducers, but even different solvents caused the
formation of the opposite enantiomers of amine 8c (Table 4, see,
together with others, entries 17–20).
3. Conclusion
In summary, our results have led us to the following conclu-
sions: (i) we have developed a small family of easily accessible
monodentate P⁄-chirogenic diamidophosphites 5a–e and 6a,b.
The advantage of these ligands is that their modular nature enables
the substituents in the 1,3,2-diazaphospholidine ring and the steric
demands to be easily and systematically varied, so their influence
on the effectiveness at transferring the chiral information can be
studied; (ii) moderate to good enantioselectivity (up to 93% ee)
was obtained in the Pd-catalyzed asymmetric allylations of
(E)-1,3-diphenylallyl acetate as a benchmark substrate. Further-
more, 5a–e and 6a,b are substantially more successful stereoselec-
tors, than the known similar monocyclic diamidophosphites LE and
LF, despite the fact that the latter have a higher diastereomeric pur-
ity;54,55,68 (iii) the results showed that the different substituents at
the C⁄-stereocenter have very marked effects on the activity and
enantioselectivity. However, the concrete substituent outcome
Please cite this article in press as: Gavrilov, K. N.; et al. Tetrahedron: Asymmetry (2013), http://dx.doi.org/10.1016/j.tetasy.2013.02.010

6
K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
4.2. General procedure for the preparation of carbamates 2a–e
4.20 (br s, 1H), 6.63 (d, J = 7.6 Hz, 2H), 6.68 (t, J = 7.5 Hz, 1H),
7.17 (t, J = 7.6 Hz, 2H). Anal. Calcd for C13H22N2: C, 75.68; H,
10.75; N, 13.58. Found: C, 75.93; H, 10.89; N, 13.67.
To a vigorously stirred solution of the relevant (S)-N-Boc-amino
acid 1a–e (15.1 mmol) and aniline (1.93 mL, 21.1 mmol) in CH2Cl2
(25 mL) was added DCC (3.43 g, 16.6 mmol) in small portions. The
solution was stirred at room temperature for 16 h, filtered on Cel-
ite, and then concentrated under vacuum (40 Torr). The crude
product was purified by flash chromatography on silica gel
(EtOAc/hexane, 4:1) and then by crystallization from heptane, to
afford the relevant compounds 2a–e in good yield.
4.3.3. (S)-N2,3,3-Trimethyl-N1-phenylbutane-1,2-diamine 3c
Slightly yellow oil (1.72 g, yield 77%). Bp 118–119 °C (1 Torr).
½
a 2D5
ꢂ
¼ þ16:7 (c 1.0, CHCl3). 1H NMR (CDCl3, 25 °C): d = 1.0 (s,
9H), 1.82 (br s, 1H), 2.25–2.33 (m, 1H), 2.51 (s, 3H), 2.91–2.99
(m, 1H), 3.23–3.31 (m, 1H), 4.21 (br s, 1H), 6.64 (d, J = 7.8 Hz,
2H), 6.70 (t, J = 7.4 Hz, 1H), 7.19 (t, J = 8.0 Hz, 2H). Anal. Calcd for
C13H22N2: C, 75.68; H, 10.75; N, 13.58. Found: C, 75.89; H, 10.79;
4.2.1. tert-Butyl (2S,3S)-3-methyl-1-oxo-1-(phenylamino)pentan-
2-ylcarbamate 2b
N, 13.39.
White powder (3.52 g, yield 76%). 1H NMR (CDCl3, 25 °C):
d = 0.91 (t, J = 7.4 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H), 1.12–1.26 (m,
2H), 1.43 (s, 9H), 1.92–2.0 (br m, 1H), 4.05–4.13 (br m, 1H), 5.24
(br d, J ꢀ8.8 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), 7.24 (t, J = 7.5 Hz,
2H), 7.48 (d, J = 7.8 Hz, 2H), 8.28 (br s, 1H). Anal. Calcd for
4.4. General procedure for the preparation of phosphorylating
reagents 4a–e
To a vigorously stirred solution of PCl3 (0.88 mL, 10 mmol) and
Et3N (3.06 mL, 22 mmol) in benzene (100 mL) was added dropwise
a solution of the relevant 1,2-diamine 3a–e (10 mmol) in benzene
(50 mL) at 0 °C over 30 min. The reaction mixture was then heated
up to boiling point, refluxed for 5 min, and cooled down to 20 °C.
Solid Et3NꢃHCl was filtered off, and the filtrate was concentrated
under vacuum (40 Torr). The residue was dried for 30 min at
10 Torr and purified by bulb-to-bulb distillation under vacuum
(1 Torr).
C17H26N2O3: C, 66.64; H, 8.55; N, 9.14. Found: C, 66.78; H, 8.61;
N, 9.07.
4.2.2. (S)-tert-Butyl 3,3-dimethyl-1-oxo-1-(phenylamino)butan-
2-ylcarbamate 2c
White powder (3.33 g, yield 72%). 1H NMR (CDCl3, 25 °C):
d = 1.06 (s, 9H), 1.42 (s, 9H), 4.03 (br d, J ꢀ9.4 Hz, 1H), 5.40 (br d,
J ꢀ9.1 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 7.27 (t, J = 8.0 Hz, 2H), 7.46
(d, J = 8.8 Hz, 2H), 7.88 (br s, 1H). Anal. Calcd for C17H26N2O3: C,
66.64; H, 8.55; N, 9.14. Found: C, 66.74; H, 8.43; N, 9.01.
4.4.1. (4S)-4-Benzyl-2-chloro-3-methyl-1-phenyl-1,3,2-diaza-
phospholidine 4a
Light yellow resin, solidifying on storage (2.41 g, yield 79%).
4.2.3. (S)-tert-Butyl 2-oxo-1-phenyl-2-(phenylamino)ethylcarb-
amate 2e
Tbath 232–235 °C (1 Torr). ½a D20
ꢂ
¼ ꢄ127:1 (c 1.0, CHCl3). 1H NMR
(CDCl3, 25 °C): d = 2.81 (d, J = 18.1 Hz, 3H), 3.17–3.25 (m, 1H),
3.26–3.35 (m, 1H), 3.36–3.44 (m, 1H), 3.51–3.59 (m, 1H), 3.79–
3.88 (m, 1H), 6.89–6.97 (m, 3H), 7.09–7.32 (m, 7H). 13C NMR
(CDCl3, 25 °C): d = 31.5 (d, 2J = 18.1 Hz, CH3N), 38.3 (d, 3J = 3.8 Hz,
CH2Ph), 53.6 (d, 2J = 9.1 Hz, CH2N), 64.1 (d, 2J = 11.3 Hz, CHN),
116.4 (d, 3J = 14.3 Hz, CHPhN), 121.5 (d, 4J = 2.2 Hz, CHPhN), 126.8
(s, CHPh), 128.8 (s, CHPh), 129.0 (s, CHPh), 129.3 (s, CHPhN), 137.4
(s, CPh), 142.7 (d, 2J = 15.1 Hz, CPhN). 31P NMR (CDCl3, 25 °C):
d = 156.7. MS (EI, 70 eV): m/z (%) = 304 (28) [M]+, 269 (100)
[MꢄCl]+. Anal. Calcd for C16H18ClN2P: C, 63.06; H, 5.95; N, 9.19.
Found: C, 63.36; H, 6.07; N, 9.38.
White powder (4.19 g, yield 85%). 1H NMR (CDCl3, 25 °C):
d = 1.42 (s, 9H), 5.35 (br s, 1H), 5.81 (br s, 1H), 7.07 (t, J = 7.4 Hz,
1H), 7.23–7.30 (m, 2H), 7.31–7.39 (m, 3H), 7.41–7.48 (m, 4H),
7.79 (br s, 1H). Anal. Calcd for C19H22N2O3: C, 69.92; H, 6.79; N,
8.58. Found: C, 69.72; H, 6.63; N, 8.62.
4.3. General procedure for the preparation of 1,2-diamines 3a–e
To a vigorously stirred cold suspension of LiAlH4 (1.02 g,
27 mmol) in THF (50 mL), 10.8 mmol of the relevant carbamates
2a–e was added portionwise. The reaction mixture was then
heated up to boiling point, refluxed for 8 h, and hydrolyzed with
2 mL of 15% aqueous KOH solution at 0 °C. The reaction mixture
was then quickly heated up to boiling point, cooled down to room
temperature, and filtered. The filter cake was washed with THF
(2 ꢁ 20 mL) and CH2Cl2 (2 ꢁ 20 mL) and the combined filtrates
were concentrated under vacuum (40 Torr). All volatiles were re-
moved under vacuum and the crude product was purified by
bulb-to-bulb distillation under vacuum (1 Torr).
4.4.2. (4S)-4-sec-Butyl-2-chloro-3-methyl-1-phenyl-1,3,2-diaza-
phospholidine 4b
Slightly yellow viscous oil (1.87 g, yield 69%). Tbath 204–207 °C
(1 Torr). ½a 2D1
ꢂ
¼ ꢄ109:8 (c 1.0, CHCl3). 1H NMR (CDCl3, 25 °C):
d = 0.87 (d, J = 6.8 Hz, 3H), 1.0 (t, J = 7.8 Hz, 3H), 1.21–1.29 (m,
1H), 1.34–1.42 (m, 1H), 1.84–1.92 (m, 1H), 2.72 (d, J = 16.1 Hz,
3H), 3.42–3.49 (m, 1H), 3.57–3.65 (m, 1H), 3.65–3.73 (m, 1H),
6.97 (t, J = 7.2 Hz, 1H), 7.04–7.10 (m, 2H), 7.30 (t, J = 7.8 Hz, 2H).
13C NMR (CDCl3, 25 °C): d = 11.5 (s, CH3), 12.2 (s, CH3), 27.2 (s,
CH2), 30.8 (d, 2J = 19.6 Hz, CH3N), 33.5 (d, 3J = 3.8 Hz, CH), 48.2 (d,
2J = 9.1 Hz, CH2N), 65.8 (d, 2J = 10.6 Hz, CHN), 116.3 (d,
3J = 15.9 Hz, CHPh), 121.3 (d, 4J = 2.3 Hz, CHPh), 129.2 (s, CHPh),
142.8 (d, 2J = 15.0 Hz, CPh). 31P NMR (CDCl3, 25 °C): d = 158.2. MS
(EI, 70 eV): m/z (%) = 270 (57) [M]+, 235 (100) [MꢄCl]+. Anal. Calcd
for C13H20ClN2P: C, 57.67; H, 7.45; N, 10.35. Found: C, 58.02; H,
7.25; N, 10.58.
4.3.1. (S)-N2-Methyl-N1,3-diphenylpropane-1,2-diamine 3a
Colorless oil (2.13 g, yield 82%). Bp 152–153 °C (1 Torr).
½
a 2D5
ꢂ
¼ þ28:7 (c 1.0, CHCl3). 1H NMR (CDCl3, 25 °C): d = 1.78 (br s,
1H), 2.49 (s, 3H), 2.80–2.88 (m, 1H), 2.90–2.97 (m, 1H), 3.01–3.12
(m, 2H), 3.18–3.26 (m, 1H), 4.28 (br s, 1H), 6.65 (d, J = 8.1 Hz,
2H), 6.75 (t, J = 7.8 Hz, 1H), 7.19–7.42 (m, 7H). Anal. Calcd for
C16H20N2: C, 79.96; H, 8.39; N, 11.66. Found: C, 79.88; H, 8.18; N,
11.59.
4.4.3. (4S)-4-tert-Butyl-2-chloro-3-methyl-1-phenyl-1,3,2-diaza-
phospholidine 4c
4.3.2. (2S,3S)-N2,3-Dimethyl-N1-phenylpentane-1,2-diamine 3b
Slightly yellow oil (1.58 g, yield 71%). Bp 110–111 °C (1 Torr).
Slightly yellow viscous oil (2.0 g, yield 74%). Tbath 215–218 °C
½
a 2D5
ꢂ
¼ þ9:2 (c 1.0, CHCl3). 1H NMR (CDCl3, 25 °C): d = 0.88
(1 Torr). ½a 2D0
ꢂ
¼ ꢄ124:5 (c 1.0, CHCl3). 1H NMR (CDCl3, 25 °C):
(d, J = 6.8 Hz, 3H), 0.94 (t, J = 7.4 Hz, 3H), 1.23–1.31 (m, 1H),
1.43–1.51 (m, 1H), 1.66–1.73 (m, 1H), 1.75 (br s, 1H), 2.39 (s,
3H), 2.51–2.59 (m, 1H), 2.82–2.90 (m, 1H), 3.12–3.20 (m, 1H),
d = 0.98 (s, 9H), 2.92 (d, J = 16.0 Hz, 3H), 3.24–3.32 (m, 1H),
3.53–3.61 (m, 1H), 3.82–3.91 (m, 1H), 7.0 (t, J = 8.0 Hz, 1H), 7.05–
7.11 (m, 2H), 7.30 (t, J = 7.9 Hz, 2H). 13C NMR (CDCl3, 25 °C):
Please cite this article in press as: Gavrilov, K. N.; et al. Tetrahedron: Asymmetry (2013), http://dx.doi.org/10.1016/j.tetasy.2013.02.010

K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
7
d = 27.7 (s, CH3), 36.7 (d, 2J = 17.1 Hz, CH3N), 46.6 (s, C), 51.9 (d,
2J = 8.1 Hz, CH2N), 73.4 (d, 2J = 11.1 Hz, CHN), 118.2 (d,
3J = 14.1 Hz, CHPh), 121.8 (d, 4J = 2.0 Hz, CHPh), 130.2 (s, CHPh),
143.2 (d, 2J = 13.1 Hz, CPh). 31P NMR (CDCl3, 25 °C): d = 161.9. MS
(EI, 70 eV): m/z (%) = 270 (68) [M]+, 235 (100) [MꢄCl]+. Anal. Calcd
for C13H20ClN2P: C, 57.67; H, 7.45; N, 10.35. Found: C, 57.46; H,
7.55; N, 10.39.
1H), 3.77–3.85 (m, 1H), 6.80 (t, J = 8.2 Hz, 1H), 6.95 (br d, J
ꢀ8.1 Hz, 2H), 7.17–7.38 (m, 7H) (minor epimer). 13C NMR (CDCl3,
25 °C): d = 31.0 (s, C(30), C(50), C(70)), 31.7 (d, 2J = 17.4 Hz, CH3N),
36.1 (s, C(40), C(60), C(100)), 39.2 (d, 3J = 4.5 Hz, CH2Ph), 45.2 (d,
3J = 8.3 Hz, C(20), C(80), C(90)), 52.8 (d, 2J = 7.6 Hz, CH2N), 61.9 (d,
2
2J = 9.1 Hz, CHN), 73.1 (d, J = 6.8 Hz, C(10)), 115.0 (d, 3J = 14.3 Hz,
CHPhN), 118.4 (d, 4J = 2.3 Hz, CHPhN), 126.3 (s, CHPh), 128.5 (s, CHPh),
128.9 (s, CHPh), 129.1 (s, CHPhN), 138.9 (s, CPh), 145.8 (d,
2J = 17.4 Hz, CPhN) (major epimer) and 31.0 (s, C(30), C(50), C(70)),
4.4.4. (4S)-2-Chloro-4-isopropyl-3-methyl-1-phenyl-1,3,2-diaza-
phospholidine 4d
2
33.1 (d, J = 31.7 Hz, CH3N), 36.2 (s, C(40), C(60), C(100)), 40.3 (s,
3
White viscous oil (1.72 g, yield 67%). Tbath 210–214 °C (1 Torr).
CH2Ph), 45.3 (d, J = 8.2 Hz, C(20), C(80), C(90)), 52.1 (d, 2J = 9.1 Hz,
½
a 2D0
ꢂ
¼ þ93:5 (c 1.0, C6H6). 1H NMR (CDCl3, 25 °C): d = 0.89 (d,
CH2N), 65.3 (d, 2J = 10.6 Hz, CHN), 68.1 (s, C(10)), 115.1 (d,
3J = 14.3 Hz, CHPhN), 118.3 (d, 4J = 1.5 Hz, CHPhN), 126.1 (s, CHPh),
128.5 (s, CHPh), 128.9 (s, CHPh), 129.3 (s, CHPhN), 139.8
(s, CPh), 146.3 (d, 2J = 15.7 Hz, CPhN) (minor epimer). MS (MALDI
TOF/TOF): m/z (%) = 439 (82) [M+H2O+H]+, 421 (80) [M+H]+,
J = 4.1 Hz, 3H), 1.0 (d, J = 7.9 Hz, 3H), 2.11–2.19 (m, 1H), 2.73 (d,
J = 16.4 Hz, 3H), 3.45–3.53 (m, 1H), 3.56–3.67 (m, 2H), 6.97 (t,
J = 8.1 Hz, 1H), 7.07 (br d, J = 8.0 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H).
13C NMR (CDCl3, 25 °C): d = 14.2 (s, CH3), 19.5 (s, CH3), 26.7 (d,
3J = 3.8 Hz, CH), 31.1 (d, 2J = 18.9 Hz, CH3N), 48.4 (d, 2J = 9.1 Hz,
CH2N), 67.1 (d, 2J = 11.3 Hz, CHN), 116.4 (d, 3J = 14.3 Hz, CHPh),
121.4 (d, 4J = 2.3 Hz, CHPh), 129.3 (s, CHPh), 142.8 (d, 2J = 15.1 Hz,
287
(100)
[(PhNCH2CH(Bn)NMe)POH+H]+,
241
(38)
[PhNHCH2CH(Bn)NHMe+H]+, 136 (10) [C10H16]+. Anal. Calcd for
C26H33N2OP: C, 74.26; H, 7.91; N, 6.66. Found: C, 74.39; H, 7.83;
N, 6.51.
C
Ph). 31P NMR (CDCl3, 25 °C): d = 158.6. MS (EI, 70 eV): m/z
(%) = 256 (33) [M]+, 221 (100) [MꢄCl]+. Anal. Calcd for
0
0
C12H18ClN2P: C, 56.14; H, 7.07; N, 10.91. Found: C, 55.86; H,
4.5.2. (4S)-4-sec-Butyl-3-methyl-1-phenyl-2-(tricyclo[3.3.1.1.3 ,7 ]-
dec-10-yloxy)-1,3,2-diazaphospholidine 5b
7.25; N, 10.69.
Colorless oil (1.31 g, yield 85%). Tbath 262–265 °C (1 Torr).
4.4.5. (4S)-2-Chloro-3-methyl-1,4-diphenyl-1,3,2-diaza-
phospholidine 4e
½
a 2D2
ꢂ
¼ ꢄ203:9 (c 0.8, C6H6). 1H NMR (CDCl3, 25 °C): d = 0.81 (d,
J = 6.9 Hz, 3H), 0.97 (t, J = 7.8 Hz, 3H), 1.19–1.28 (m, 1H), 1.36–
1.46 (m, 1H), 1.63 (br s, 6H), 1.72–1.85 (br m, 2H), 1.92 (br s,
4H), 2.05–2.12 (m, 1H), 2.13 (br s, 3H), 2.55 (d, J = 16.2 Hz, 3H),
3.07–3.15 (m, 1H), 3.35–3.65 (m, 2H), 6.81 (t, J = 7.5 Hz, 1H), 7.02
(br d, J = 8.1 Hz, 2H), 7.16–7.26 (m, 2H) (major epimer) and 0.94
(d, J = 7.0 Hz, 3H), 1.01 (t, J = 7.7 Hz, 3H), 1.19–1.28 (m, 1H),
1.36–1.46 (m, 1H), 1.63 (br s, 6H), 1.72–1.85 (br m, 2H), 1.92 (br
s, 4H), 2.05–2.12 (m, 1H), 2.13 (br s, 3H), 2.77 (d, J = 13.2 Hz, 3H),
3.35–3.65 (m, 3H), 6.66 (t, J = 7.8 Hz, 1H), 7.00 (br d, J = 8.0 Hz,
2H), 7.16–7.26 (m, 2H) (minor epimer). 13C NMR (CDCl3, 26 °C):
d = 11.4 (s, CH3), 12.6 (s, CH3), 27.5 (s, CH2), 31.0 (s, C(30), C(50),
C(70)), 31.1 (d, 2J = 13.6 Hz, CH3N), 34.1 (d, 3J = 3.8 Hz, CH), 36.2
Slightly yellow resin (2.06 g, yield 71%). Tbath 241–244 °C
(1 Torr). ½a 2D0
ꢂ
¼ ꢄ154:4 (c 0.9, CHCl3). 1H NMR (CDCl3, 25 °C):
d = 2.57 (d, J = 16.6 Hz, 3H), 3.62–3.70 (m, 1H), 4.06 (br t,
J = 11.9 Hz, 1H), 4.60–4.68 (m, 1H), 6.99 (t, J = 7.8 Hz, 1H), 7.06
(d, J = 7.9 Hz, 2H), 7.30 (t, J = 7.9 Hz, 2H), 7.34–7.45 (m, 5H). 13C
NMR (CDCl3, 25 °C): d = 31.5 (d, 2J = 17.4 Hz, CH3N), 57.2 (d,
2J = 9.2 Hz, CH2N), 67.7 (d, 2J = 10.6 Hz, CHN), 116.2 (d,
3J = 15.1 Hz, CHPhN), 121.5 (d, 4J = 1.9 Hz, CHPhN), 127.8 (s, CHPh),
128.6 (s, CHPh), 129.0 (s, CHPhN), 129.4 (s, CHPh), 137.9 (d,
3J = 4.5 Hz, CPh), 142.6 (d, 2J = 15.2 Hz, CPhN). 31P NMR (CDCl3,
25 °C): d = 154.8. MS (EI, 70 eV): m/z (%) = 290 (14) [M]+, 255
(100) [MꢄCl]+. Anal. Calcd for C15H16ClN2P: C, 61.97; H, 5.55; N,
9.64. Found: C, 62.11; H, 5.61; N, 9.34.
3
(s, C(40), C(60), C(100)), 45.3 (d, J = 7.5 Hz, C(20), C(80), C(90)), 47.3
(d, 2J = 8.3 Hz, CH2N), 63.5 (d, 2J = 9.8 Hz, CHN), 73.5 (d,
2J = 6.8 Hz, C(10)), 114.8 (d, 3J = 15.8 Hz, CHPh), 118.2 (d,
4J = 2.3 Hz, CHPh), 128.9 (s, CHPh), 145.6 (d, 2J = 17.1 Hz, CPh) (major
epimer) and 12.5 (s, CH3), 13.2 (s, CH3), 27.1 (s, CH2), 30.8 (s, C(30),
C(50), C(70)), 31.3 (d, 2J = 29.5 Hz, CH3N), 33.5 (d, 3J = 6.0 Hz, CH),
4.5. General procedure for the preparation of ligands 5a–e and
6a,b
3
To a vigorously stirred solution of the relevant phosphorylating
reagents 4a–e (4 mmol) and Et3N (0.61 mL, 4.4 mmol) in toluene
(10 mL) was added dropwise a solution of adamantan-1-ol or
methanol (4 mmol) in toluene (10 mL) at 0 °C over 20 min. The
reaction mixture was then heated up to boiling point, refluxed
for 10 min, and cooled down to 20 °C. Solid Et3NꢃHCl was then re-
moved by filtration. The resulting solution was filtered through a
short plug of aluminum oxide, and the solvent evaporated under
reduced pressure (40 Torr). The residue was purified by bulb-to-
bulb distillation under vacuum (1 Torr, 5b, 5c, 5d, 6a, and 6b) or
by flash chromatography on aluminum oxide (EtOAc/hexane, 1:1,
5a and 1:3, 5e).
36.3 (s, C(40), C(60), C(100)), 45.2 (d, J = 7.5 Hz, C(20), C(80), C(90)),
47.7 (d, 2J = 8.3 Hz, CH2N), 67.9 (d, 2J = 10.6 Hz, CHN), 73.7 (d,
2J = 5.3 Hz, C(10)), 116.0 (d, 3J = 13.6 Hz, CHPh), 118.4 (d,
4J = 2.3 Hz, CHPh), 129.3 (s, CHPh), 144.9 (d, 2J = 15.5 Hz, CPh) (minor
epimer). MS (MALDI TOF/TOF): m/z (%) = 387 (100) [M+H]+, 207
(42) [PhNHCH2CH(sec-Bu)NHMe+H]+, 136 (11) [C10H16]+. Anal.
Calcd for C23H35N2OP: C, 71.47; H, 9.13; N, 7.25. Found: C, 71.62;
H, 9.23; N, 7.19.
0
0
4.5.3. (4S)-4-tert-Butyl-3-methyl-1-phenyl-2-(tricyclo[3.3.1.1.3 ,7 ]-
dec-10-yloxy)-1,3,2-diazaphospholidine 5c
Colorless oil (1.27 g, yield 82%). Tbath 276–279 °C (1 Torr).
½
a 2D5
ꢂ
¼ þ238:1 (c 1.0, CHCl3). 1H NMR (CDCl3, 25 °C): d = 0.99 (s,
0
0
4.5.1. (4S)-4-Benzyl-3-methyl-1-phenyl-2-(tricyclo[3.3.1.1.3 ,7
]
9H), 1.59 (br s, 6H), 1.84 (br s, 4H), 1.87–2.95 (br m, 2H), 2.10
(br s, 3H), 2.90 (d, J = 16.1 Hz, 3H), 3.06–3.14 (m, 1H), 3.56–3.64
(m, 1H), 3.69–3.76 (m, 1H), 6.77 (t, J = 8.0 Hz, 1H), 6.95 (br d,
J = 7.9 Hz, 2H), 7.18–7.26 (m, 2H) (major epimer) and 0.90 (s,
9H), 1.61 (br s, 6H), 1.83 (br s, 4H), 1.87–2.95 (br m, 2H), 2.10
(br s, 3H), 2.70 (d, J = 12.2 Hz, 3H), 3.06–3.14 (m, 1H), 3.56–3.64
(m, 1H), 3.69–3.76 (m, 1H), 6.79 (t, J = 7.8 Hz, 1H), 6.99 (br d,
J = 8.0 Hz, 2H), 7.18–7.26 (m, 2H) (minor epimer). 13C NMR (CDCl3,
25 °C): d = 27.4 (s, CH3), 30.9 (s, C(30), C(50), C(70)), 36.3 (s, C(40),
C(60), C(100)), 39.7 (d, 2J = 45.3 Hz, CH3N), 43.9 (d, 3J = 3.8 Hz, C),
dec-10-yloxy)-1,3,2-diazaphospholidine 5a
Colorless viscous oil (1.36 g, yield 81%). ½a D22
¼ þ254:4 (c 1.0,
ꢂ
CHCl3). 1H NMR (CDCl3, 25 °C): d = 1.63 (br s, 6H), 1.91 (br s, 4H),
1.93–2.05 (br m, 2H), 2.15 (br s, 3H), 2.72 (d, J = 15.0 Hz, 3H),
3.07–3.15 (m, 1H), 3.45–3.55 (m, 2H), 3.57–3.65 (m, 1H),
3.77–3.85 (m, 1H), 6.80 (t, J = 8.2 Hz, 1H), 6.95 (br d, J ꢀ8.1 Hz,
2H), 7.17–7.38 (m, 7H) (major epimer) and 1.65 (br s, 6H), 1.91
(br s, 4H), 1.93–2.05 (br m, 2H), 2.15 (br s, 3H), 2.53 (t, J = 9.3 Hz,
1H), 2.84 (d, J = 12.0 Hz, 3H), 3.19–3.30 (m, 2H), 3.57–3.65 (m,
Please cite this article in press as: Gavrilov, K. N.; et al. Tetrahedron: Asymmetry (2013), http://dx.doi.org/10.1016/j.tetasy.2013.02.010

8
K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
3
45.1 (d, J = 8.3 Hz, C(20), C(80), C(90)), 49.8 (d, 2J = 7.6 Hz, CH2N),
4J = 3.0 Hz, CHPhN), 127.4 (s, CHPh), 128.5 (s, CHPh), 128.6 (s,
CHPhN), 129.0 (s, CHPh), 141.9 (s, CPh), 145.4 (d, 2J = 16.2 Hz, CPhN
(minor epimer). MS (MALDI TOF/TOF): m/z (%) = 425 (100)
[M+H2O+H]+, 273 (94) [(PhNCH2CH(Ph)NMe)POH+H]+, 227 (76)
[PhNHCH2CH(Ph)NHMe+H]+, 136 (15) [C10H16]+. Anal. Calcd for
2
73.1 (d, J = 6.6 Hz, C(10)), 75.6 (d, 2J = 10.6 Hz, CHN), 115.7 (d,
)
3J = 13.6 Hz, CHPh), 118.3 (d, 4J = 2.3 Hz, CHPh), 128.9 (s, CHPh),
145.7 (d, 2J = 16.0 Hz, CPh) (major epimer) and 27.0 (s, CH3), 31.1
2
(s, C(30), C(50), C(70)), 35.7 (d, J = 14.3 Hz, CH3N), 36.1 (s, C(40),
C(60), C(100)), 43.6 (d, 3J = 4.5 Hz, C), 45.2 (d, J = 8.3 Hz, C(20),
C25H31N2OP: C, 73.87; H, 7.69; N, 6.89. Found: C, 74.01; H, 7.74;
N, 7.08.
3
C(80), C(90)), 48.6 (d, 2J = 6.8 Hz, CH2N), 71.6 (d, 2J = 10.6 Hz, CHN),
2
73.3 (d, J = 6.7 Hz, C(10)), 116.3 (d, 3J = 14.3 Hz, CHPh), 118.7 (d,
4J = 2.3 Hz, CHPh), 128.8 (s, CHPh), 143.7 (d, 2J = 15.1 Hz, CPh) (minor
epimer). MS (EI, 70 eV): m/z (%) = 386 (7) [M]+, 329 (100) [Mꢄt-
Bu]+. Anal. Calcd for C23H35N2OP: C, 71.47; H, 9.13; N, 7.25. Found:
C, 71.77; H, 8.97; N, 7.36.
4.5.6. (4S)-4-Benzyl-2-methoxy-3-methyl-1-phenyl-1,3,2-diaza-
phospholidine 6a
Colorless oil (1.07 g, yield 89%). Tbath 213–216 °C (1 Torr).
½
a 2D2
ꢂ
¼ ꢄ117:6 (c 1.0, CHCl3). 1H NMR (CDCl3, 25 °C): d = 2.42–
2.51 (m, 1H), 2.71–2.78 (m, 1H), 2.82 (d, J = 13.6 Hz, 3H), 3.36 (d,
J = 8.4 Hz, 3H), 3.38–3.64 (m, 2H), 3.87–3.95 (m, 1H), 6.83 (br t, J
ꢀ8.1 Hz, 1H), 6.97 (br t, J ꢀ8.0 Hz, 2H), 7.17–7.28 (m, 5H), 7.29–
7.36 (m, 2H) (major epimer) and 2.42–2.51 (m, 1H), 2.71–2.78
(m, 1H), 2.87 (d, J = 13.2 Hz, 3H), 3.28 (d, J = 8.8 Hz, 3H), 3.38–
3.64 (m, 2H), 3.87–3.95 (m, 1H), 6.83 (br t, J ꢀ8.1 Hz, 1H), 6.97
(br t, J ꢀ8.0 Hz, 2H), 7.17–7.28 (m, 5H), 7.29–7.36 (m, 2H) (minor
epimer). 13C NMR (CDCl3, 25 °C): d = 25.3 (d, 2J = 18.2 Hz, CH3N),
35.9 (d, 3J = 2.8 Hz, CH2Ph), 50.0 (d, 2J = 2.2 Hz, CH3O), 52.5 (d,
2J = 7.7 Hz, CH2N), 64.3 (d, 2J = 10.5 Hz, CHN), 125.5 (d,
3J = 19.9 Hz, CHPhN), 130.8 (d, 4J = 1.4 Hz, CHPhN), 139.6 (s, CHPh),
142.1 (s, CHPh), 142.6 (s, CHPh), 142.7 (s, CHPhN), 153.5 (s, CPh),
0
0
4.5.4. (4S)-4-Isopropyl-3-methyl-1-phenyl-2-(tricyclo[3.3.1.1.3 ,7 ]-
dec-10-yloxy)-1,3,2-diazaphospholidine 5d
Colorless oil (1.34 g, yield 90%). Tbath 249–253 °C (1 Torr).
½
a 2D0
ꢂ
¼ þ221:2 (c 1.0, CHCl3). 1H NMR (CDCl3, 26 °C): d = 0.80 (d,
J = 4.1 Hz, 3H), 0.97 (d, J = 8.0 Hz, 3H), 1.60 (br s, 6H), 1.70–1.82
(br m, 2H), 1.88 (br s, 4H), 2.0–2.08 (m, 1H), 2.12 (br s, 3H), 2.53
(d, J = 16.1 Hz, 3H), 3.07–3.15 (m, 1H), 3.37–3.53 (m, 2H), 6.78 (t,
J = 8.1 Hz, 1H), 7.01 (br d, J = 7.9 Hz, 2H), 7.22 (t, J = 7.9 Hz, 2H) (ma-
jor epimer) and 0.94 (d, J = 4.0 Hz, 3H), 0.99 (d, J = 8.1 Hz, 3H), 1.60
(br s, 6H), 1.70–1.82 (br m, 2H), 1.89 (br s, 4H), 2.0–2.08 (m, 1H),
2.12 (br s, 3H), 2.78 (d, J = 12.2 Hz, 3H), 3.19–3.27 (m, 1H), 3.37–
3.53 (m, 2H), 6.78 (t, J = 8.1 Hz, 1H), 6.96 (br d, J = 8.2 Hz, 2H), 7.22
(t, J = 7.9 Hz, 2H) (minor epimer). 13C NMR (CDCl3, 25 °C): d = 13.9
162.2 (d, 2J = 15.4 Hz, CPhN
) (major epimer) and 28.9 (d,
2J = 34.1 Hz, CH3N), 36.0 (s, CH2Ph), 47.8 (d, 2J = 2.8 Hz, CH3O),
52.7 (d, 2J = 7.7 Hz, CH2N), 65.7 (d, 2J = 9.4 Hz, CHN), 125.7 (d,
3J = 19.8 Hz, CHPhN), 130.9 (s, CHPhN), 139.5 (s, CHPh), 142.1 (s,
CHPh), 142.6 (s, CHPh), 142.6 (s, CHPhN), 153.9 (s, CPh), 161.8 (d,
2J = 13.8 Hz, CPhN) (minor epimer). MS (EI, 70 eV): m/z (%) = 301
(9) [M+H]+, 269 (22) [MꢄOMe]+, 209 (100) [MꢄBn]+, 179 (87)
[MꢄOMeꢄBn+H]+. Anal. Calcd for C17H21N2OP: C, 67.98; H, 7.05;
N, 9.33. Found: C, 67.68; H, 6.90; N, 9.46.
3
(s, CH3), 19.6 (s, CH3), 26.7 (d, J = 4.0 Hz, CH), 30.8 (s, C(30), C(50),
2
C(70)), 31.0 (d, J = 17.1 Hz, CH3N), 35.9 (s, C(40), C(60), C(100)), 45.0
(d, J = 8.1 Hz, C(20), C(80), C(90)), 47.0 (d, 2J = 8.1 Hz, CH2N), 64.4
3
(d, 2J = 10.1 Hz, CHN), 72.7 (d, 2J = 6.0 Hz, C(10)), 114.6 (d,
3J = 16.1 Hz, CHPh), 117.9 (d, 4J = 1.5 Hz, CHPh), 128.7 (s, CHPh),
145.8 (d, 2J = 18.1 Hz, CPh) (major epimer) and 16.6 (s, CH3), 19.6
(s, CH3), 29.5 (s, CH), 30.7 (s, C(30), C(50), C(70)), 34.2 (d,
2J = 40.2 Hz, CH3N), 36.0 (s, C(40), C(60), C(100)), 44.9 (d, 3J = 9.1 Hz,
C(20), C(80), C(90)), 48.1 (d, 2J = 8.1 Hz, CH2N), 69.1 (d, 2J = 10.2 Hz,
CHN), 72.5 (d, 2J = 7.0 Hz, C(10)), 115.5 (d, 3J = 14.1 Hz, CHPh), 118.1
4.5.7. (4S)-4-sec-Butyl-2-methoxy-3-methyl-1-phenyl-1,3,2-
diazaphospholidine 6b
(d, 4J = 2.3 Hz, CHPh), 128.6 (s, CHPh), 145.6 (d, 2J = 16.2 Hz, CPh
)
Colorless liquid (0.91 g, yield 85%). Tbath 182–185 °C (1 Torr).
(minor epimer). MS (MALDI TOF/TOF): m/z (%) = 411 (18) [M+K]+,
373 (36) [M+H]+, 239 (100) [(PhNCH2CH(i-Pr)NMe)POH+H]+, 193
(53) [PhNHCH2CH(i-Pr)NHMe+H]+, 136 (13) [C10H16]+. Anal. Calcd
for C22H33N2OP: C, 70.94; H, 8.93; N, 7.52. Found: C, 71.21; H,
8.75; N, 7.29.
½
a 2D2
ꢂ
¼ ꢄ105:0ꢅ (c 1.0, CH2Cl2). 1H NMR (CDCl3, 25 °C): d = 0.76 (d,
J = 6.8 Hz, 3H), 0.99 (t, J = 7.4 Hz, 3H), 1.18–1.27 (m, 1H),
1.33–1.44 (m, 1H), 1.81–1.89 (m, 1H), 2.73 (d, J = 13.2 Hz, 3H),
3.34 (d, J = 8.0 Hz, 3H), 3.45–3.56 (m, 2H), 3.69–3.77 (m,
1H), 6.81–6.87 (m, 1H), 7.05 (br t, J ꢀ8.5 Hz, 2H), 7.20–7.29 (m,
2H) and 0.97 (d, J = 6.8 Hz, 3H), 0.99 (t, J = 7.4 Hz, 3H), 1.18–1.27
(m, 1H), 1.33–1.44 (m, 1H), 1.81–1.89 (m, 1H), 2.65 (d,
J = 13.6 Hz, 3H), 3.24 (d, J = 8.8 Hz, 3H), 3.25–3.33 (m, 2H), 3.41
(t, J = 9.4 Hz, 1H), 6.81–6.87 (m, 1H), 7.05 (br t, J ꢀ8.5 Hz, 2H),
7.20–7.29 (m, 2H) (mixture of epimers). 13C NMR (CDCl3, 25 °C):
d = 10.9 (s, CH3), 12.4 (s, CH3), 26.8 (s, CH2), 29.8 (d, 2J = 20.4 Hz,
CH3N), 34.0 (d, 3J = 3.4 Hz, CH), 47.9 (d, 2J = 8.7 Hz, CH2N), 51.2
(d, 2J = 1.9 Hz, CH3O), 65.2 (d, 2J = 11.7 Hz, CHN), 114.4 (d,
3J = 14.4 Hz, CHPh), 119.0 (d, 4J = 2.3 Hz, CHPh), 129.0 (s, CHPh),
144.2 (d, 2J = 16.8 Hz, CPh) and 10.9 (s, CH3), 12.0 (s, CH3), 27.2 (s,
CH2), 33.5 (d, 2J = 41.0 Hz, CH3N), 35.2 (s, CH), 48.2 (d, 2J = 8.8 Hz,
CH2N), 48.9 (s, CH3O), 66.1 (d, 2J = 9.1 Hz, CHN), 114.9 (d,
3J = 13.3 Hz, CHPh), 118.9 (s, CHPh), 128.9 (s, CHPh), 143.5 (d,
0
0
4.5.5. (4S)-3-Methyl-1,4-diphenyl-2-(tricyclo[3.3.1.1.3 ,7 ]dec-10-
yloxy)-1,3,2-diazaphospholidine 5e
White waxy solid (1.25 g, yield 77%). ½a D20
¼ þ276:0 (c 0.9,
ꢂ
CHCl3). 1H NMR (CDCl3, 25 °C): d = 1.65 (br s, 6H), 1.82–1.94 (br
m, 2H), 1.99 (br s, 4H), 2.17 (br s, 3H), 2.40 (d, J = 16.1 Hz, 3H),
3.24–3.32 (m, 1H), 3.90–3.99 (m, 1H), 4.52–4.59 (m, 1H), 6.81
(t, J = 7.9 Hz, 1H), 7.0 (br t, J = 7.9 Hz, 2H), 7.24 (t, J = 8.0 Hz,
2H), 7.27–7.43 (m, 5H) (major epimer) and 1.61 (br s, 6H),
1.82–1.94 (br m, 2H), 1.99 (br s, 4H), 2.11 (br s, 3H), 2.60 (d,
J = 12.4 Hz, 3H), 3.61 (t, J = 8.0 Hz, 1H), 3.90–3.99 (m, 1H), 4.38–
4.46 (m, 1H), 6.81 (t, J = 7.9 Hz, 1H), 7.0 (br t, J = 7.9 Hz, 2H),
7.24 (t, J = 8.0 Hz, 2H), 7.27–7.43 (m, 3H), 7.54 (d, J = 8.0 Hz, 2H)
13
(minor epimer). C NMR (CDCl3, 25 °C): d = 31.1 (s, C(30), C(50),
2J = 15.2 Hz, CPh
) (mixture of epimers). MS (EI, 70 eV): m/z
2
C(70)), 31.8 (d, J = 15.9 Hz, CH3N), 36.2 (s, C(40), C(60), C(100)),
(%) = 266 (11) [M]+, 235 (39) [MꢄOMe]+, 209 (100) [Mꢄsec-Bu]+.
Anal. Calcd for C14H23N2OP: C, 63.14; H, 8.70; N, 10.52. Found: C,
63.28; H, 8.76; N, 10.25.
45.3 (d, J = 8.3 Hz, C(20), C(80), C(90)), 56.8 (d, 2J = 8.3 Hz, CH2N),
3
65.8 (d, 2J = 9.1 Hz, CHN), 73.5 (d, J = 6.8 Hz, C(10)), 114.8 (d,
2
3J = 15.1 Hz, CHPhN), 118.5 (d, 4J = 1.8 Hz, CHPhN), 127.8 (s, CHPhN),
128.1 (s, CHPh), 128.9 (s, CHPh), 129.0 (s, CHPh), 140.7 (d,
3J = 4.5 Hz, CPh), 145.9 (d, 2J = 17.4 Hz, CPhN) (major epimer) and
31.0 (s, C(30), C(50), C(70)), 32.7 (d, 2J = 34.7 Hz, CH3N), 36.3 (s,
4.6. Catalytic reactions
4.6.1. Pd-catalyzed allylic sulfonylation of (E)-1,3-diphenylallyl
acetate 7 with sodium para-toluene sulfinate
A solution of [Pd(allyl)Cl]2 (0.0019 g, 0.005 mmol) and the
appropriate ligand (0.01 mmol or 0.02 mmol) in THF (1.5 mL)
3
C(40), C(60), C(100)), 45.4 (d, J = 6.8 Hz, C(20), C(80), C(90)), 56.2
(d, 2J = 8.1 Hz, CH2N), 68.7 (d, 2J = 10.6 Hz, CHN), 72.8 (d,
2J = 6.7 Hz, C(10)), 116.5 (d, 3J = 13.6 Hz, CHPhN), 118.9 (d,
Please cite this article in press as: Gavrilov, K. N.; et al. Tetrahedron: Asymmetry (2013), http://dx.doi.org/10.1016/j.tetasy.2013.02.010

K. N. Gavrilov et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
13. Falciola, C. A.; Alexakis, A. Eur. J. Org. Chem. 2008, 3765–3780.
9
was stirred for 40 min. Next, (E)-1,3-diphenylallyl acetate
(0.05 mL, 0.25 mmol) was added and the solution stirred for
15 min, after which sodium para-toluene sulfinate (0.089 g,
0.5 mmol) was added and the reaction mixture stirred for a further
48 h, quenched with brine (3 mL), and extracted with THF
(3 ꢁ 2 mL). The organic layer was washed with brine (2 ꢁ 2 mL)
and dried over MgSO4. The solvent was evaporated at reduced
pressure (40 Torr). Crystallization of the residue from EtOH, fol-
lowed by desiccation in vacuum (10 Torr, 12 h), gave (E)-1,3-di-
phenyl-3-tosylprop-1-ene 8a as white crystals. The enantiomeric
excess of 8a was determined by HPLC.
14. Hargaden, G. C.; Guiry, P. J. Chem. Rev. 2009, 109, 2505–2550.
15. Bini, L.; Muller, C.; Vogt, D. Chem. Commun. 2010, 8325–8334.
16. Tolstikov, A. G.; Khlebnikova, T. B.; Tolstikova, O. V.; Tolstikov, G. A. Russ. Chem.
Rev. 2003, 72, 803–822.
17. Zhou, Q.-L. Privileged Chiral Ligands and Catalysts; Wiley-VCH: Weinheim, 2011.
18. Dieguez, M.; Ruiz, A.; Claver, C. Dalton Trans. 2003, 2957–2963.
19. Teichert, J. F.; Feringa, B. L. Angew. Chem., Int. Ed. 2010, 49, 2486–2528.
20. Ansell, J.; Wills, M. Chem. Soc. Rev. 2002, 31, 259–268.
21. Alexakis, A.; Benhaim, C. Eur. J. Org. Chem. 2002, 19, 3221–3236.
22. Molt, O.; Schrader, T. Synthesis 2002, 2633–2670.
23. Reetz, M. T.; Mehler, G.; Meiswinkel, A.; Sell, T. Tetrahedron Lett. 2002, 43,
7941–7943.
24. Dieguez, M.; Pamies, O.; Claver, C. Tetrahedron: Asymmetry 2004, 15, 2113–
2122.
25. Gavrilov, K. N.; Bondarev, O. G.; Polosukhin, A. I. Russ. Chem. Rev. 2004, 73, 671–
699.
26. Jerphagnon, T.; Renaud, J.-L.; Bruneau, C. Tetrahedron: Asymmetry 2004, 15,
2101–2111.
4.6.2. Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl
acetate 7 with dimethyl malonate
A solution of [Pd(allyl)Cl]2 (0.0019 g, 0.005 mmol) and the
appropriate ligand (0.01 mmol or 0.02 mmol) in the appropriate
solvent (1.5 mL) was stirred for 40 min. Next, (E)-1,3-diphenylallyl
acetate (0.05 mL, 0.25 mmol) was added and the solution stirred
for 15 min. Dimethyl malonate (0.05 mL, 0.44 mmol), BSA
(0.11 mL, 0.44 mmol), and potassium acetate (0.002 g) were added.
The reaction mixture was then stirred for 48 h, diluted with CH2Cl2
or THF (2 mL), and filtered through a thin layer of silica gel. The fil-
trate was evaporated at reduced pressure (40 Torr) and dried in
vacuum (10 Torr, 12 h) affording a residue containing (E)-dimethyl
2-(1,3-diphenylallyl)malonate 8b. In order to evaluate the ee and
conversion, the residue obtained was dissolved in an appropriate
eluent mixture (8 mL) and a sample was taken for HPLC analysis.
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A solution of [Pd(allyl)Cl]2 (0.0019 g, 0.005 mmol) and the
appropriate ligand (0.01 mmol or 0.02 mmol) in the appropriate
solvent (1.5 mL) was stirred for 40 min. Next, (E)-1,3-diphenylallyl
acetate (0.05 mL, 0.25 mmol) was added and the solution stirred
for 15 min, then freshly distilled pyrrolidine (0.06 mL, 0.75 mmol)
was added. The reaction mixture was stirred for 48 h, diluted with
CH2Cl2 or THF (2 mL) and filtered through a thin layer of silica gel.
The filtrate was evaporated at reduced pressure (40 Torr) and dried
in vacuum (10 Torr, 12 h) affording a residue containing (E)-1-(1,3-
diphenylallyl)pyrrolidine 8c. In order to evaluate the ee and
conversion, the residue obtained was dissolved in an appropriate
eluent mixture (8 mL) and a sample was taken for HPLC analysis.
Acknowledgements
The reported study was partially supported by RFBR, research
project Nos. 11-03-00347-a and 12-03-31205-mol-a.
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Please cite this article in press as: Gavrilov, K. N.; et al. Tetrahedron: Asymmetry (2013), http://dx.doi.org/10.1016/j.tetasy.2013.02.010